be underdiagnosed (2,3). The clinical suspicion of PE isessential to its diagnosis, which is based initially on thephysician's clinical assessment of the patient for signsand/or symptoms of venous thrombosis and PE supplemented, as needed, by studies such as a chest radiograph,EKGandarterialbloodgases. Unfortunately,neitherthechest radiograph,EKG or arterialblood gases provide thephysician with sufficient information to make or excludethe diagnosis of PE. The chest radiographserves to exdude disease entities that mimic PE, but findings such asoigemia (Westermark's sign), vascular redistribution orpleural-based areas of increased opacity (Hampton'shump) do not have sufficient sensitivity or specificity toobviate further evaluation (4). Following careful clinical

evaluation and assessment of the presence of any predisposing factors to PE (5), the clinician determines the mostlikely diagnosis and, if PE is suspected, initiates further PEevaluation through such imaging studies as radionucideventilation-perfusion(V/Q) scintigraphyand/orpulmonaiyangiography (6, 7).

V/Qscintigraphyhasplayeda majorrolein theevaluation of patients with suspected PE for more than two decades, depicting the sequelae of PE as a V/Q mismatch(8,9). Such a mismatch, especially when solitary, is nonspecific, and various interpretive schemes or algorithmshave been advanced (10—13)to improve the sensitivity andspecificity of V/Q scintigraphy in the detection of pulmonaw embolism. These schemes rely on the natural histoiyof pulmonaiy thromboembolism, in which clot fragmentation in the right heart induces multivessel segmental embolization of the pulmonary vasculature with preservationof segmental ventilation (14). Although this approach hasits limitations because of interpretive underestimation ofsegmental size and nonrecognition of some segmental defects (15,16), such schemes have demonstrableclinical utility. Retrospective analysis of the Prospective Investigationof PulmonaryEmbolismDiagnosis (PIOPED)scintigraphiccriteria for V/Q scan interpretationdemonstrated that theoriginal prospective criteria should be modified by categorizing a single moderate perfusion defect as intermediaterather than low probability and extensive matched V/Qdefects with clear chest radiographas low rather than in

To assess the use of modifiedPIOPEDSCintigraphiCcritenaforlung scan (V/Q) interpretationto detect pulmonary embolism(PE), we prospectivelyapplied these critena in suspected PEpatients referredforWQfrom9/i/92 to 217/94.PIOPEDcritenawere mOdifiedby placinga moderatesegmentalperfusicnmismatch in the intermediateinstead of lowprobabilityof PE catsgoryand usingthe “stripesign.―Methods: Patientswere studiedby six-viewV/Q imagingusing 74 MBq(2 mCi) @‘9c-MMfollowed by i48-370 MBq (4-10 mCi) @rc-DTPAaerosol,contrast pulmonaryselective angiographyand Dopplersonographywithleg compression as needed. Patients underwentfollow-up(mean 13.9 mo) to detect subsequent thromboembolicevents. In this study group, 1000 pabents were studied by WQfollowed by angiography in 133 patients. Results: The distribution of V/Q-assigned PE probabilities was: high probability 5.7%,intermediate i7.4%, low 41.4% and normal 35.5%. Group Apatients (133) underwent angiography, which resulted in thedeterminabon of a 27.i% PE prevalence. Group B patients (867)did not have angiograms; the clinical prevalence of PE was7.5%.Inthe totalstudypopulation,the positivepredictivevalueofa highprobabilityVIQstudyforPE(iO.i%prevalence)was98.2%,intermediateprObabilftyWQstudyfor PE was 24.1%anda low probabilitystudy for PE was only 0.5%. ConclusIon:MOdifiedPIOPEDWQ interpretationcriteriaaffordbetter ang@proven PE discnmination between intermediate (31.8% PE preyaience) and low (5.5%PE prevalence)probabilityV/Q resultsthan reported for PIOPEDintermediate(32.6%PE prevalence)and low (16.3% PE prevalence) proba@lftyWQ interpretadoncriteria.

Key Words: ventilation-perfusionimaging;PIOPEDcriteria;technetium-99m-MAA; technebum-99m-DTPA aerosol; pulmonary angiography

J NucIMed1995;36:1573—1578

he incidence ofvenous thrombosisand pulmonaryembolism (PE) has remained constant for 30 yr (1). Althoughdeath from PE for in-patientsis declining, PE continues to

ReonivedJune 8, 1994;revisionacceç@edOd@27, 1994.For correspondenceor reprintscontact John E. Freitas,MD,RadiologyDe

partment, St Joseph Mercy Hospital, 5301 E. Huron Rwer Dr., Mn Arbor, Ml48106.

ClinicalUse MOdifiedPIOPEDCriteria•Freitas at al. 1573

Modffied PIOPED Criteria Used in ClinicalPracticeJohn E. Freitas, Michael G. Sarosi, Christopher C. Nagle, Maiy E. Yeomans, Anne E. Freitas andJack E. Juni

Department ofRadiolo@j', St. Joseph Mercy Hospital Ann Arbor, Michigan; RadiOlOgy Department, University ofWashingtonMedical Center, Seattle, Washington;and Nuclear Medicine Department, lVilhiamBeaumontHospitalRoyal OaIçMichigan

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TABLE 1Asalgnment of WQ Proba@Iftyof Pulmonary Embol@m

Rules: AiwaysbeginwithProbability= Normal.Conthuetothenextquestbnunl#yoriare instructedtoSTOP.Oncea givenProbability(PROB)hasbeenasalgned,ftmayon@iincrease,neverdecrease.Foronedefecttobe“muchlargerthan―another,itshouldbe tw@e

as large.A >25% segmental defect exhibitingthe ‘@sthpesign―withinthat segment Is ignored.

Begin with Perfusion Scan Probability = Normal.1. Are there any 0 defe@s?

No -@PROB= NORMALSTOP.Yes -@PROB = LOW.Continueto questkn 2.

2. Are there any 0 defects >25% of a segment?No-@PROB= LOW.STOP.Yes -â€C̃ontkiueto question3?

3. Arethereanychest radiographabnormalitiesoverlappingQ defects (>25%of segment)?No-@PROB= LOW.Contkiuetoquestk?n5.Yes -@Cor;thuetoquestion4.

4. Are all0 defects >25% of a segment matched by much largerchest radiographdefects?No—@PROB= INTERMEDIATE.Continuetoquestion5.Yes -@PROB = LOW STOP.

5. Are there any 0 defects >25% of a segment not matched by chest radiographabnormality?No-@STOP.Yes -+ Continueto questk@n6.

Perform VentilatIonScan6. AreALL>25%ofa segment0 defectsmatchedbyV defectsdespitenormalchestradiograph?

No-@Conthuetoquestion7.Yes -@PROB@ LOW.Continueto questkn 9?

7. Are there 2 large 0 defects “muchlargerthan―correspondingV or chest radiographdefects?Answerno ifV and chest radiographare normalin defect regionsor onlyone large defect Is present.

No-@PROB= INTERMEDIATE.Continuetoquestion8.Yes -@PROB = HIGH.STOP.

8. Arethere>2 segmentalequivalent0 defectswithnormalV and normalchest radiograph?No-@PROB= INTERMEDLATE.STOP.Yes -@PROB = HIGH.STOP.

9. Do matched V and 0 defects cover >50% of the combined lung fields?No-+ PROB= LOW.STOP.Yes -* PROB = INTERMEDIATE.STOP.

determinate probability (17). A subsection of this analysisalso confirmed the validity of the “stripesign―(18) as anindication that a segmental perfusion defect showing thesign was not likely due to PE (19).

To determine if the new knowledge gleaned from retrospective analysis of the PIOPED study would improve theclinical utility of V/Q scintigraphy in our clinical practice,we conducted the following prospective study.

METHODS

From 9/1/92 to 2/7/94, we prospectivelyappliedmodifiedPIOPEDcriteriatoourscintigraphicinterpretationofV/Qstudiesperformed on 1000patients (593women, 407 men)with suspectedPEwhowerereferredto theradiologydepartment.Anadditionalseven patients with a lung or hilar mass and ten patients whounderwentpulmonaryangiographywithoutpriorV/Q scintigraphywereexcludedfromfurtheranalysis.Themedicalrecordsofthese 1000patientswere reviewedto determinethe presence orabsence of PE. During this time interval, the hospital's primaryand secondary discharge diagnoses of more than 34,000 in-patients revealed 101patientswith PE. The diagnosisof PE was feltto be establishedby: (a)detectionof PEby pulmonaryangiographyor (b)thepresenceof venousthrombosis,anabnormallungperfusion study and clinical assessment and confirmation ofPE bytheattendingpuhnonologist.

Scintigraphic TechniquesPerfusionstudieswere performedwith 74MBq(2mCi) @“Tc

MAA. A standard six-view (no LAO or RAO) studywas obtainedwith500,000ct/viewusingaparallel-hole,low-energy,all-purposecollimatoron a gammacamera. If the perfusionwas abnormal,aventilationstudywasthenperformedinthestandardfashionwith

@Fc-pentetate(DTPA) using an Aerovent (MediNuclear, Baldwin Park, CA) aerosol delivery system that provided 148—370MBq (4—10mCi) of aerosol to the patient to achieve at least threeto fourtimesthecountrateachievedduringtheperfusionimages.Ventilationimages(500,000eta/view)were obtainedin the sameprojectionsas the abnormalperfusion images. In 402 patients,ventilationimageswere not obtainedbecausethe perfusionimages were normal,ventilation images were not possible or ventilationimageswerenot indicated(e.g., matchedperfusiondefectwithchestradiographabnormality).

Chest radiographs, portable AP or standard PA and lateral,wereobtainedon allpatientswithin24hrof theV/Qscanandallyb studies were interpreted together with the chest radiograph.

Sclntigraphic InterpretationTheV/Qstudieswere classifiedintofourcategories:normal,

low,intermediateor highprobabilityusingthe algorithmshowninTable1. Thisalgorithm,thepatient'scurrentchestx-rayandananatomical lung segment reference chart (20) were used by eachobserverto determinethe probabilityassignmentof each V/Q

1574 TheJournalof NudearMedicine•Vol.36 •No. 9 •September1995

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Scancategory(Probability) Cuffent study@(%)PIOPED @ar@yt(%)High6

(4.5)117(15.5)Intermediate91(68.4)331(43.8)Low36(27.1)250(33.1)NOrmal/AlmOSt

normal0(0)57(6.6)from

133patients.from775patients.

Scancategory

(Probability)PE

present(%)

CurrentstudyPE

present(%)

PIOPEDstudyHigh5

(83.3)102(87.9)Intermediate29(31.8)105(32.6)Low2

(5.5)39(16.3)

study. Seven patients unable to perform a satisfactory ventilationstudy but who had at least one moderate or large segmentalperfusion defect were designated as having intermediate probability of PE. V/Q studies were interpreted by multiple observers (17total), but 782 studies were read by four experienced observers.The formal V/Q interpretationissued by a staff physician at thetime of the V/Q procedurewas used in this analysis.

Pulmonary AnglographySixexperiencedangiographersperformedpulmonaryangiogra

phybythetransfemoralapproachusingselectiveandsubselectivearterial contrast injectionsin multipleprojectionsas needed toadequatelyassess the perfusiondefects shown on the V/Q study.Bilateral pulmonary angiography was performed in almost allpatients, unless PE was readilyapparentin the first lung studied,as suggested by the V/Q report, at which point the angiogramstudy was terminated.The presence of a vascular cut-offor intraluminalfillingdefect confirmedthe diagnosisofPE. The formalangiogramreport issued at the time of the procedurewas used inthis analysis.

CompressIon Doppler SonographyCompression doppler sonography of the calf, popliteal fossa

and thigh was performed in the usual manner. The presence ofvenous thrombosiswas confirmedby the lack of compressibilityof the vein or direct visualization of intraluminalthrombus.

Patient Follow-upThe hospital inpatient and outpatient records were reviewed

retrospectively from 9/1/92 to 9/30/94 through a computerizedsearch for a primaryor secondary diagnosisofvenous thrombosisor PE. Patients diagnosed as havingvenous thrombosisor PE atdischarge or during a visit to the clinic were cross-referenced withour prospective study patient population to determine the frequency of the development or recurrence of these diagnoses inour study group.

RESULTS

The distributionof V/Q assigned PE probabilities our1000 patients using modified PIOPED V/Q interpretationcriteriawas: 5.7% for high, 17.4%for intermediate,41.4%for low and 35.5% for normal, respectively. Pulmonaryangiography was performed in 133 patients (Group A) butnot in the remaining867 patients (GroupB). Angiographywas performedmore frequently(52.3%)in patientswith anintermediate probability V/Q study but only infrequently(8.9%)inpatientswithhighorlowprobabilitystudies.Thediagnosis of PE was made in 101 patients: 36 by angiography and 65 by a combinationoflung scan, sonography andclinical assessment.

Group A patients (PE prevalence of 27.1%) had a V/Qdistribution of 6 for high probability, 91 for intermediateprobability and 36 for low probability studies as comparedto the PIOPED distribution (Table 2). In the 42 patientswith high or low probability studies, the V/Q result wasdiscordant with their pretest clinical assessment and angiography was ordered. Angiography confirmed PE in 5 of6 high probability, 29 of 91 intermediate studies and 2 of 36low probabilitystudies as compared to the PIOPED study(Table 3).

TABLE 2wQScanCategoryDistribution:CurrentVersusPIOPED

Shidy

Modified PIOPED V/Q interpretation criteria providebetter angio-provenPE discriminationbetween intermediate (31.8% PE prevalence) and low probability (5.5% PEprevalence) Yb results than reported for PIOPED intermediate (32.6%PE prevalence) and low (16.3% PE preyalence) probability V/Q interpretive criteria (p < 0.001).This better discrimination is accomplished in part by recategorizing 14 V/Q scans demonstrating a single moderateV/Qmismatchfromthelowprobability(underPIOPED)tothe intermediateprobabilitycategory (17). Six of these 14patients (42.9%)had angio-proven PE (Fig. 1). Similarly,five patients with a soitaiy segmental or multisegmentalmismatch exhibiting the stripe sign were recategorizedfrom intermediate (under PIOPED) to low probability;none of these patients had angio-proven PE.

GroupB patientsdid not have angiogramsbut had a V/Qdistributionof 51 high (5.8%), 83 intermediate(9.6%), 378low (43.6%) and 355 normal (40.9%) probability studies.Sixty-five of these patients were diagnosed as having PE(PEprevalence7.5%)basedonahighprobabilitylungscanand concordant clinical assessment in 51 and an intermediate probability scan with positive sonogram for venousthrombosis and concordant clinical assessment in 14.

In the total study population (PE prevalence 10.1%), thepositive predictive value (PPV) of a high probability V/Qstudy for PE was 98.2%, 24.1% for an intermediateprobability V/Q study, 0.5% for a low probability study.

Compression doppler sonographywas performedin 195patients: 25 patientswith high probability,65 patients withintermediate probability, 84 patients with low probabilityand21 patientswith normalV/Q scans. Venous thrombosiswas present in 45 patients (17with highprobability,18withintermediate probability, 8 with low probability and 2 with

TABLE 3Comparisonof AngiographicFindingswithWQ Scan Category

I 575ClinicalUse MOdifiedPIOPED Criteria•Freitas at ai.

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A

L

POST

AL

B

POST

then to aerosol ventilation V/Q images perform better inthe clinical arenathanPIOPED criteria.The interpretation

A criteriaalgorithm(Table1)usedinthisstudydoesnotdiffer in content from the modified PIOPED criteria proposed initiallyby one of the authors (JEJ)in 1991 (13) butis presented in a dichotomous question and answer formatto facilitate its use by the staff physicians in our practicewith limited V/Q scan interpretation experience. The V/Qscan distribution for this total study population is signifIcantly different from that reported in the PIOPED studybut is similar to that reported from other non-universitysettings where the majority of patients referred for V/Qstudies are not in-patients at the time of referral (21).

Unlike the PIOPED study, the patients in our Groups Aand B represent considerable selection bias as the patientsin Group A presented difficultdiagnostic and therapeuticdecisions for their referring physicians necessitating angiography for clarification of their clinical status. All 42patients in GroupA with high or low probabilityV/Q stud

R iesdemonstratedmajordiscordancebetweentheirreferring physician's pretest clinical assessment of the likeihood of PE and the reported V/Q probability.

In this population, the high probabilityand normalscanresults seen in 412 patients were concordant with the finalclinical diagnosis in all but one patient. This patient's study(Fig. 2) was read as high probability of PE incorrectly,since clearly, on review, this V/Q study has only a low or,at most, an intermediateprobabilityof PE. Similarly, oneof the two patients with a low probability study, subsequently confirmed to have PE by angiography, was interpreted incorrectly (Fig. 3). As exemplified by these twointerpretive errors, despite supposed adherence to a defined diagnostic algorithm, it is well recognized that erro

FIGURE1. (A)SeleCtedperfusionimagesdemonstratea mod- neous interpretationsoccur if proper attention to detail iserate nght posterior basal perfusion defect (arrows). (B) Selected not maintained (22).ventilation images demonstrate mismatched ventilation to this seg- We believe that the lung scan should be reviewed by thement.

angiographer prior to performing pulmonary angiographyand that the lung with the most suspicious defects shouldbe catheterized first. This approachshortens the angiogra

normalV/Q scans). In the latter6 mo of our study, patients phy procedure time significantly in many patients and rewith an intermediate probability V/Q study, a positive duces the contrast load in compromised patients. The predoppler study for venous thrombosis and concordant cm- cisc segmental location of the perfusiondefects seen on theical assessment for PE underwent angiography less fre- lung scan must be considered by the angiographer whenquently for confirmation of PE since the angiographic re- interpreting the angiogram. In 3 of our 36 positive angiosults would not affect the referring physician's decisions on gr@, the preliminary impression of “negativeangio

therapeutic regimen. gram―was reversed when PE was subsequently identifiedNine patients (0.9%) were found to have thromboem- after direct comparison to the pre-angiogram lung scan.

bolic events during the mean follow-up period of 13.9 mo. We believe that our V/Q technique has advantages overSix patients had venous thrombosis only, two patients had that used in the original PIOPED study (12). Performing

venous thrombosis and PE and one had PE. All three the perfusion prior to the ventilation study permits thepatients with PE, however, had had PE diagnosed initially venifiation study to be tailored for optimal positioning toduringthe prospective study and were felt to have recur- dete@i@e the presence or absence of V/Q mismatches.rences (one presumed treatment failure). Also, direct overlay of the ventilation image on the perfu

sion image allows detection of previously unrecognizedDISCUSSION perfusion defects, especially in the posterior basal, lingular

This prospective study demonstrates that modified and anteriorsegments. Such perfusion defects may not bePIOPED interpretation criteria applied to perfusion and well demonstratedon xenon images acquiredpriorto per

1576 The Journalof NudearMedicine•Vol.36 •No. 9 •September1995

RLAT@

RLAT RPO

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B

I

C

IA

fusion imaging. The better quality of our postperfusionventilation studies achieved with our sequential approachenables the readerto ascertain that subtle 0.5—1.0segmental mismatch(es) are indeed present in certain patients.

We do not believe that our 13.3%angiographyrate sig

ANT RLAT

nificantly underestimates the true prevalence of PE in thispatient population, as suggested by the lower PE prevalence in GroupB versus GroupA. Retrospective review of272 consecutive patients at this institution studied prior to9/1/92usingaerosolventilationinitiallyandthena perfusion V/Q scan demonstrated almost identical results fordetermining PE prevalence (10%), despite a 19.5% angiographyrate. In addition,our total study groupdemonstratedonly a 0.9% venous thrombosis or PE event rate during ourfollow-up period. It is unlikely that a significantnumberofpatients with untreated, undiagnosed thromboembolic disease would have such a low incidence of recurrence if leftuntreated. Our follow-up event rate is slightly lower thanthat reportedby others and may possibly reflect a lack ofcomplete knowledge of our study population since somepatients with subsequent venous thrombosis and/or PErecurrence may have sought treatment elsewhere duringthe follow-up period (23,24). It more likely reflects, however, the lower overall prevalence of venous thrombosisand PE in our patient populationas compared to a university hospital setting.

CONCLUSION

In this prospective study, we have demonstrated that aperfusion test followed by a ventilation V/Q study using

LLAT modifiedPIOPEDinterpretationcriteriabetterdiscriminates between the intermediate and low probability scancategories than PIOPED interpretationcriteria.This resultwas achieved through an interpretationcriteria algorithm,despite a variety of readers with variable V/Q interpretation experience. We recommend the diagnostic approachshown in Figure 4 to our referring physicians. This approach is similar to the diagnostic strategy suggested recently by Stein et al. (25) but emphasizes compressionsonography in preference to impedance plethysmographybecause of sonography's greater sensitivity and predictivevalue (24).

RPO POSTI

FIGURE 3. Aperfusion-ontystudyinwhichthe decreased perfuslontothe entirenghtupperlobeand nghtsuperiorsegmentwasnotacknowledged. A ventilationstudy should have been performed butwas not because of this oversight and subsequent angiographydemonstrateda nonocdusWethrombusinthe ilghtmainpulmonarywtsry.

1577ClinicalUse MOdifiedPIOPEDCriteria•Freitas at al.

POST RPO

1@R L@4R

POST RPO@1@

FIGURE2. (A)AP chest radiographdemonstratesrightlowerlobeopacification.(B)Selectedpienarimegesdemonstratematchedperfusiondefectw@istripesign (arrows).(C)Seiectedventilationimagesdemonstratethat ventilationis muchworsethan perfusion.

LPO

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Very 1@ Pro1@bi@1itv

Suap.at.d Pg

Dk@t x-ray go Ye.& P.rfuai@i@ Reaent Pg, ? r@zrr.na. e- Anqiobang c@n

@ >_@@ YesVentilation@ p.rfu.icn d.tect e-@

other 1k J.@@ High Prc@bi1ityPoreni

Look forPro@bi1ity@ Th@t for Pg

Koder&t. or high@clinical auapicion?/ @.—@-————---,—@-—

Look for other 1k . lag ultraaonmi

— for VT/―@\+@fOr VT

_io Treat for VT

aI@PgI@@Dx

14. UPEF. Urokinasepulmonaryembolismtrial: phase 1 results—acooperative study.JA@MA1970;214:2163—21fl.

15. Morrell NW, RobertsCM, JonesBE, et al. The anatomyof radioisotopelungscanning.JNUC1Med199233:676-683.

16.MorrellNW,N@jranKS,JonesBE,etal.Theunderestimationofsegmentaldefect size in radionuclidelungscanning.INuciMed 1993;34:370-374.

17.GottschalkA, SostmanHD, ColemanRE,etaLVentilation-perfusionscintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphiccriteriaand interpretations.INuciMed 1993;34:1119-1126.

18.SostmanHD,GottschalkA. Thestripesign:anewsignfordiagnosisofnonembolicdefectson pulmonaryperfusionScintigraphy.Radiology1982;142:737—741.

19.SostmanHD, GottschalkA. Prospectivevalidationof the stripesigninventilation-perfusionSCintigraphy.Radiology1992;184:455—459.

20. LansingAWA,van BeekEJR, DemersC, et al. Ventilation-perfusionlungscanningand the diagnosisof pulmonaryembolism:improvementof observer agreementby the use of a lung segment referencechart. ThmmbHaemostas 199268:245—249.

21. Lowe VI, BUI1ard0, ColemanRE. V/Q lungscan probabffitycategorydistrthutionin universityand communityhospitals[Abstractj.INUCIMed199334:17P.

22. Scott JA, PalmerEL Do diagnosticalgorithmsalwaysproducea uniformlungscan interpretation?JNuc/Med 1993;34:661-665.

23. Hull RD, HirshJ, Carter CJ, et aL Diagnosticefficacyof impedanceplethysmographyfor clinicallysuspected deep-veinthrombosis:a randomizedtrial.Ann Intern Med 1985;102:21—28.

24. He@jboerH, BullerHR, LeasingAWA,et aLA comparisonof real-timecompressionultrasonographywith impedanceplethysmographyfor the diagnosisofdeep-veinthrombosisin symptomaticoutpatients.NEngIJMed1993329:1365-1369.

25. Stein PD, Hull 1W, Saltzman HA, Piano 0. Strategy for diagnosis ofpatientswith suspectedacute pulmonaryembolism.C!zest1993;103:1553-1559.

1578

FiGURE4. Diegnostlc scheme forthe evaluationofpatientswithsuspectedpulmonaryembolism.

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The Journal of Nudear Medicine•Vol.36 •No. 9 •September 1995

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1995;36:1573-1578.J Nucl Med.   John E. Freitas, Michael G. Sarosi, Christopher C. Nagle, Mary E. Yeomans, Anne E. Freitas and Jack E. Juni  Modified PIOPED Criteria Used in Clinical Practice

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